Cyproterone Acetate

PEP Topic

Hot Flashes

Description

Cyproterone acetate is a synthetic steroidal antiandrogen drug used to treat prostate cancer. It suppresses androgen hormones by inhibiting growth of testosterone-sensitive cells. An acetate salt, the drug works by binding to androgen receptors to prevent receptor activation. Additionally, this drug reduces luteinizing hormone via the pituitary gland, which reduces androgen secretion in the testes and overall serum testosterone levels. It has weak progestational and antineoplastic activities. It has been studied for its effect in reducing hot flashes in patients with cancer.

A systematic review of the literature of hot flash interventions for men treated for prostate cancer found that some hormonal agents, including cyproterone acetate, were able to decrease hot flashes by at least 75% but produced severe side effects. All studies were too limited to evaluate safety and long-term risks of treatment.

Search Strategy:

INCLUSION CRITERIA All studies were randomized controlled studies (RCT) that addressed hot flashes (HF) in men with any stage of prostate cancer, treated with androgen deprivation therapy either medically or surgically. The studies addressed treatment for hot flashes where the main outcomes were frequency of hot flushes, distress from hot flushes, or hot flash score.

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: 252

METHOD OF STUDY EVALUATION The Jadad score was used to assess the quality of the randomized controlled trial (RCT), on a five-point scale, and the QUORUM guidelines for systematic review were considered.

This summary did not include the measures that were used by the participants in reporting their hot flashes: i.e, diaries, skin temperature measurements, QOL surveys.

Sample Characteristics:

KEY SAMPLE CHARACTERISTICS: Samples included men with prostate cancer who had undergone surgical or medical castration and were currently experiencing hot flushes.

Phase of Care and Clinical Applications:

PHASE OF CARE Active Treatment

APPLICATIONS Late Effects and Survivorship; Elderly Care

Results:

In the five studies analyzed, the treatments that were studied included cyproterone acetate (CA), megestrol acetate (MA), gabapentin, transdermal clonidine, and diethylstilbestrol (DES). Unfortunately, none of the studies analyzed the same treatment. Because the studies looked at different interventions to relieve hot flushes (HF) in castrated men with prostate cancer, it was not possible to combine the studies to strengthen the outcomes. The studies' outcomes demonstrated varying degrees of success in relieving the hot flushes: Cyproterone acetate 100 mg, once per day, yielded 75% fewer HF than placebo (p<0.001), and 100% of men on CA had a 50% or greater reduction of mean number of HF, compared to placebo group. Megestrol acetate 20 mg, twice per day, yielded an 80% reduction of the median number of HF compared to a 19% reduction in the placebo group (p<0.001), an 87% reduction of median HF score vs. a 16% reduction for placebo (p<0.001), and a 50% or greater reduction of median number of HF (p<0.001) reported by 79% of MA group and 12% of placebo group. Gabapentin (4 schedules) achieved a 45.5% reduction of the median number of HF with 900mg gabapentin per day vs. 21.5% with placebo (p=0.02). Transdermal clonidine demonstrated no difference between the treated group and placebo. Diethylstilbestrol (1 mg) yielded a 100% reduction in the median number of HF vs.13% with placebo. 100% of DES and 14% of placebo reported a 50% or greater reduction of the median number of HF.

Conclusions:

The systematic review of studies on treatment approaches to managing hot flushes in men after castration for prostate cancer showed very few such studies. Only five RCT studies were identified, and none of them analyzed the same treatment approach. Several of the studies that were presented demonstrated successful treatment approaches, including DES as the most effective, followed closely by MA and CA. However, these medications are linked to side effects that are not well tolerated by all patients.

Limitations:

Only five RCT studies were identified, and none of them analyzed the same treatment approach.

Nursing Implications:

Large randomized placebo controlled studies are needed to clarify the data and provide clearer direction to managing HF in men who have been castrated as a treatment for prostate cancer. The summary, although providing insight for possible medical management, addressed only briefly the drop-out rates due to side effects. Further investigations of the drop-out subgroup could explore correlations among the medications to reveal unacceptable side effects in managing the participants’ hot flash symptoms. Further investigations comparing medications used and providing more specific information about measurements of QOL and hot flash reporting by participants are warranted.

Sample Characteristics:

KEY DISEASE CHARACTERISTICS All had prostate cancer treated with hormonal therapy for at least 6 months. All had experienced 14 or more hot flushes in the week before study entry

Study Design:

Double blind randomized controlled trial

Measurement Instruments/Methods:

Daily hot flush diary

European Organization for Research and Treatment of Cancer Quality of life questionnaire ( EORTC-QLC 30)

Results:

Patients in the medroxyprogesterone group had higher hot flash scores at baseline. The reduction in daily hot flush scores at 4 weeks was significantly lower for all 3 groups (p<.0001). Improvements were significantly lower in the venlafaxine group than either of the other 2 groups ( p = .0006), and patients ratings of efficacy of treatment showed that significantly fewer patients in the venlafaxine group rated the treatment as good ( p<.0001) compared to the other 2 groups. Adverse events related to the study drugs were not significantly different between groups, though cyproterone led to a non significantly higher number of vascular adverse events. The most frequent adverse events were gastrointestinal, including pain, constipation, diarrhea and nausea. GI events were more frequent with venlafaxine.

Conclusions:

Men with significant hot flushes during androgen suppression for prostate cancer appeared to respond better to cyproterone acetate and medroxyprogesterone acetate than to venlafaxine

Limitations:

Baseline sample/group differences of import

Risk of bias (no control group)

Other limitations/*explanation No control or placebo group precluded observation of placebo effect. The sample was limited to patients who sought treatment for hot flashes. This was a short follow up period - longer term efficacy is not known. Effects of hormonal treatment for hot flashes on prostate cancer are not known.

Nursing Implications:

It appears that hormonal treatment is more effective in than venlafaxine for management of hot flashes in patients who are receiving androgen suppression for prostate cancer. Results also showed that many men did not seek treatment for this problem, suggesting that nurses may need to directly assess these patients for problems with hot flash symptoms. Effects of steroidal anti androgens on prostate cancer are not clear, and patients receiving both androgen suppression and cyproterone or medroxyprogesterone could have increases in prostate specific antigen concentrations.